This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We used selective neocortical and region-specific gene deletion, we examined the role of prelimbic BDNF of transgenic mouse lines. We found our cortex-specific BDNF knockout mice have deficits in freezing behavior (expressing learned fear) following fear conditioning, whereas innate fear behavior, locomotor, sensory and spatial learning tasks remain unaffected. Additionally, these mice were then retrained 30min after administration of either a potent TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) or vehicle, using a new, different CS tone and training context. The Cre+, cortical knockout mice injected with vehicle still showed freezing deficits compared to their litter mate controls. In contrast, Cre+, cortical knockout mice injected with the TrkB agonist, 7,8-DHF, now had equivalently robust fear expression as the control mice. For even greater region specific targeting, we induced prelimbic cortical BDNF deletions by Cre-expressing lentiviral infections into the prelimbic cortex in BDNF-floxed mice. Consistent with our earlier findings, these prelimbic BDNF deletion mice have robust deficits in consolidation of cued fear, but no effects on acquisition of cued fear, expression of unlearned fear, sensorimotor function, spatial learning, and extinction. Our current studies in neocortical BDNF knockout mice may provide further evidence that short-term memory following fear conditioning appears intact, suggesting prelimbic BDNF is critical for consolidation of learned fear memories, but is not required for unlearned fear or extinction of fear.